Gastrointestinal Pathology. Группа авторов
Gastroesophageal Reflux Disease
Definition, General Features, Predisposing Factors
The chronic regurgitation of gastroduodenal juice into the esophagus causes gastroesophageal reflux disease (GERD). The mucosal injury results from the effects of refluxed gastric acid, bile, pepsin, and duodenal contents that overwhelm the normal protective antireflux barriers, such as esophageal acid clearance and mucosal resistance. Risk factors and predisposing conditions include obesity, diet, sedentary lifestyle, tobacco and alcohol use, hiatus hernia, reduced lower esophageal sphincter tone, loss of esophageal peristaltic function, gastric hypersecretory states, and delayed gastric emptying. Symptomatic GERD is prevalent worldwide, with considerable geographic variation. Prevalence estimates are approximately 20% in North America and Europe, with only East Asia showing estimates <10%.
Clinical Features and Endoscopic Characteristics
There are several endoscopic classifications of gastroesophageal reflux disease (Figure 2.9). The Los Angeles Classification divides esophagitis into four grades:
Grade A: one or more mucosal breaks, each no longer than 5 mm.
Grade B: at least one mucosal break more than 5 mm long, but not continuous between the tops of 2 mucosal folds.
Figure 2.9 Endoscopic appearance of erosive esophagitis in a patient with gastroesophageal reflux disease.
Grade C: at least one mucosal break that is continuous between the tops of 2 or more mucosal folds, but which is not circumferential.
Grade D: a circumferential mucosal break, erosions and ulceration, often resulting in scarring and stenosis if the reflux is recurrent.
Mucosal bridges and esophagogastric fistulae may be encountered.
The endoscopic findings in reflux esophagitis have been classified into three main stages: active, healing, and scarring. Relapse and healing occur repeatedly in patients with gastroesophageal reflux disease (GERD), and a mixture of the stages is often seen in biopsy specimens.
Microscopic Features
The typical features of GERD are basal cell layer hyperplasia, papillary elongation, dilated intercellular spaces (intercellular edema/spongiosis), and intraepithelial inflammation, including neutrophils, eosinophils, and mononuclear cells (Table 2.2; Figures 2.10, 2.11). However, none of these features is specific for this diagnosis.
The proliferative epithelial changes are more common than inflammatory infiltration. Basal cell hyperplasia is diagnosed when the thickness of the basal layer exceeds 15% in a well‐oriented section. Papillary elongation, defined as extending >50% of the epithelial thickness, should also be only assessed in well‐oriented sections. Finally, in minimal GERD, dilated intercellular spaces in the basal and parabasal areas may be the only finding.
Esophageal squamous mucosa normally contains few or no inflammatory cells and the inflammatory infiltrate in GERD is highly variable. The presence of occasional eosinophils is typical of GERD, although large numbers of intraepithelial eosinophils mimicking eosinophilic esophagitis may be identified. Notably, eosinophils are not found in all GERD biopsies and can be seen in asymptomatic patients. Neutrophils may be present, and are more numerous in areas of erosion and ulceration. Lymphocytes, often with irregular nuclear contours (squiggle cells), are usually scattered through the epithelium. Finally, severe inflammation with ulceration may be associated with inflammatory pseudotumor formation, with marked atypia of the reactive stromal cells.
Table 2.2 Histologic features of GERD.
| Basal cell hyperplasia (>15%) |
| Papillary elongation (>50%) |
| Dilated intercellular spaces (spongiosis) |
| Intraepithelial inflammation Neutrophils |
| Eosinophils |
| Mononuclear cells |
Figure 2.10 Characteristic appearance of low‐power view of reflux esophagitis with basal cell hyperplasia, elongation of papillae, lymphocytic and eosinophilic infiltrate.
In practice, the report should provide a descriptive summary of the histologic features and injury patterns present, as well as their severity. A note can be added to state that the findings are compatible with reflux injury pattern in the appropriate clinical setting.
Figure 2.11 High‐power magnification of reflux esophagitis with basal cell hyperplasia, spongiosis, and eosinophilic infiltrate.
Differential Diagnosis
Clinical
Clinically, erosive esophagitis from GERD is typically in the lower third of the esophagus and contiguous with the gastroesophageal junction as opposed to other inflammatory or infectious etiologies that may occur more proximally. The presence of a normal distal esophagus with more proximal inflammation virtually excludes GERD‐associated inflammation. Typical symptoms are heartburn and regurgitation. Ph‐ metry (monitoring the acid reflux events by a wired or wireless sensor in the distal esophagus) can be used in challenging cases but is rarely necessary with obvious symptoms and when esophagitis is seen.
Microscopic
As none of the histologic features are specific for GERD, other etiologies such as infection, eosinophilic esophagitis, iatrogenic injuries, Crohn's disease, and inflammatory skin disorders involving the esophagus may enter into the differential diagnosis.
The presence of large numbers of neutrophils in the superficial epithelium should suggest the possibility of fungal infection or superinfection, and special stains (PAS‐diastase, GMS) should be performed to exclude Candida organisms. Large numbers of intraepithelial eosinophils raising the possibility of eosinophilic esophagitis and correlation with clinical findings and PPI treatment status are required (see Section “Eosinophilic Esophagitis”). Numerous intraepithelial lymphocytes, if predominant, may suggest an alternative diagnosis such as lymphocytic esophagitis or lichen planus‐associated esophagitis (see Sections “Lymphocytic Esophagitis” and “Dermatological Diseases Involving the Esophagus”).
Ulceration with regenerative squamous epithelial atypia